转录因子BMI1增加了口腔表皮中的缺氧信号
Jorge Baquero1, Xiao-Han Tang1, Annalisa Ferrotta2
1Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Biochimica et biophysica acta. Molecular basis of disease
|April 10, 2024
概括
在舌头干细胞中的高BMI1表达触发低氧信号和代谢转移,影响口腔上皮的生长,并可能导致口腔癌的发展.
科学领域:
- 口腔生物学 口腔生物学
- 干细胞生物学 干细胞生物学
- 癌症研究 癌症研究
背景情况:
- 舌头上皮依靠基底干细胞 (SCs) 进行更新.
- BMI1 (B-淋巴瘤Mo-MLV插入区域1) 对于SCs至关重要,也是口腔癌中的生物标志物.
- 之前的工作建立了一个小鼠模型 (KrTB) 来控制舌头SCs中的Bmi1表达.
研究的目的:
- 为了研究BMI1在正常舌头上皮的功能作用.
- 阐明BMI1影响口腔上皮细胞的分子机制.
- 评估BMI1过度表达对SC增殖和细胞代谢的影响.
主要方法:
- 利用可诱导多西环素的转基因小鼠模型 (KrTB) 针对向的Bmi1过度表达.
- 进行全基因组转录组学来分析基因表达变化.
- 采用染色体免疫沉 (ChIP) 来识别Bmi1结合部位.
- 评估了细胞系中的SC增殖,氧化应激和代谢参数.
主要成果:
- Bmi1过度表达诱导了与缺氧相关的基因表达,而没有实际的缺氧.
- 观察到高水平的缺氧诱导因子-1α (HIF1α) 和它的目标.
- BMI1与HIF1A和RELA的促进体直接相关 (p65).
- 在Bmi1-过度表达的上皮质中检测到增加的SC增殖和氧化应激.
- 过度表达BMI1促进了葡萄糖分解,并减少了口腔角质细胞的氧气消耗.
结论:
- 口腔表皮中的BMI1过度表达驱动了缺氧信号通路.
- 这导致代谢重编程,有利于糖解.
- 这些发现突显了BMI1在调节正常口腔上皮质平衡中的作用,以及它对口腔状细胞癌的潜在影响.
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